STRATA: Natalizumab (Tysabri) Re-Initiation of Dosing

• Sponsor: Biogen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00297232
• Collaborator: (none)
• Enrollment: 1,094
• Locations: 112
• Arm: 1
• Duration (Months): 97
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objectives for the initial treatment period of this study are to further evaluate the safety of natalizumab monotherapy by evaluating the risk of hypersensitivity reactions and immunogenicity following re-exposure to natalizumab and confirming the safety of switching from interferon (IFN), glatiramer acetate, or other multiple sclerosis (MS) therapies to natalizumab. The primary objective for the long-term treatment period of this study is to evaluate the long-term impact of natalizumab monotherapy on the progression of disability measured by Expanded Disability Status Scale (EDSS) changes over time.

Condition or Disease	Intervention/Treatment	Phase
Relapsing-Remitting Multiple Sclerosis	Drug: Natalizumab	Phase 3

Detailed Description

Study 101-MS-322 (NCT00306592) was conducted to evaluate the safety of natalizumab monotherapy following re-exposure to natalizumab in former clinical trial participants in Studies C-1801 (NCT00027300), C-1802 (NCT00030966), and C-1803 (NCT00097760) and included subjects in North America. In parallel with the conduct of that study, this study (101-MS-321 [NCT00297232]) was initiated for participants in Europe and the rest of the world. In addition, after 48 weeks, participants from 101-MS-322 (NCT00306592) could enter study 101-MS-321 (NCT 00297232), which was considered the Long-Term Treatment Period of 101-MS-322 (NCT00306592).

The primary purpose and primary outcome for both studies are identical; therefore, the combined long-term data from both studies are presented. (Combined Week 48 data from both studies are presented in the 101-MS-322 [NCT00306592] record.)

Study Design

• Study Type: Interventional
• Actual Enrollment: 1094 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, Extension Study to Evaluate the Safety and Tolerability of Natalizumab Following Re-Initiation of Dosing in Multiple Sclerosis Subjects Who Have Completed Study C-1801, C-1802, C-1803, or C-1808 and a Dosing Suspension Safety Evaluation
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Natalizumab 300 mg intravenous (IV) infusions once every 4 weeks for up to 480 weeks	Drug: Natalizumab; Other Names: Tysabri (BG00002)

Outcome Measures

Primary Outcome Measures

1. Time to 24-week Confirmed Expanded Disability Status Scale (EDSS) Progression [up to 480 weeks]

   Time to 24-week confirmed EDSS progression in participants with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 24-week EDSS progression was defined as ≥ 0.5 point increase from a baseline EDSS ≥ 6.0, or ≥ 1.0 point increase from a baseline EDSS ≥ 1.0 and < 6.0, or ≥ 1.5 point increase from a baseline EDSS of 0, all sustained for 24 weeks.

2. Time to 48-week Confirmed EDSS Progression [up to 480 weeks]

   Time to 48-week confirmed EDSS progression in particpants with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 48-week EDSS progression was defined as ≥ 0.5 point increase from a baseline EDSS ≥ 6.0, or ≥ 1.0 point increase from a baseline EDSS ≥ 1.0 and < 6.0, or ≥ 1.5 point increase from a baseline EDSS of 0, all sustained for 48 weeks.

3. Time to 24-week Confirmed EDSS Improvement Where Baseline ≥ 2.0 [Up to 480 weeks]

   Time to 24-week confirmed EDSS improvement in subjects with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 24-week EDSS improvement is defined as ≥ 1.0 point decrease from baseline sustained for 24 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria

• MS subjects who completed Study C-1801 (NCT00027300), C-1802 (NCT00030966), or C-1803 (NCT00097760) and a Dosing Suspension Safety Evaluation (neurological examination or a magnetic resonance imaging scan) or participated in the IMA 04001 (STARS) Study

• Subjects who are considered by the Investigator to be free of signs and symptoms suggestive of progressive multifocal leukoencephalopathy and willing to discontinue and remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFN-beta and glatiramer acetate) while being treated with natalizumab during the study.

• In addition, subjects who completed 48 weeks of treatment in Study 101-MS-322 (NCT00306592) in Canada will be allowed to enter this study at the start of the long-term treatment period (Week 52 - 480).

Key Exclusion Criteria

• Considered by the Investigator to be immunocompromised

• History of persistent anti-natalizumab antibodies, based upon testing from prior natalizumab studies

• History of any major disease or malignancy

• Discontinued natalizumab in a previous study due to allergic reaction

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Camperdown		Australia	2050
2	Research Site	Heidelberg		Australia	3084
3	Research Site	Parkville		Australia	3050
4	Research Site	Brugge		Belgium	8000
5	Research Site	Brussels		Belgium	1070
6	Research Site	Charleroi		Belgium	6000
7	Research Site	Diepenbeek		Belgium	3590
8	Research Site	Melsbroek		Belgium	1820
9	Research Site	Sijsele		Belgium	8340
10	Research Site	Vancouver	British Columbia	Canada	V6T 2B5
11	Research Site	Halifax	Nova Scotia	Canada	B3H IV7
12	Research Site	Kingston	Ontario	Canada	K7L 2V7
13	Research Site	London	Ontario	Canada	N6A5A5
14	Research Site	New York	Ontario	Canada	M4N 3M5
15	Research Site	Ottawa	Ontario	Canada	K2G6E2
16	Research Site	Toronto	Ontario	Canada	M5B 1W8
17	Research Site	Gatineau	Quebec	Canada	J8Y 1W7
18	Research Site	Greenfield Park	Quebec	Canada	J4V 2H1
19	Research Site	Montreal	Quebec	Canada	H3A2B4
20	Research Site	Brno		Czech Republic	625 00
21	Research Site	Brno		Czech Republic	656 91
22	Research Site	Hradec Kralove		Czech Republic	500 05
23	Research Site	Olomouc		Czech Republic	775 20
24	Research Site	Ostrava		Czech Republic	708 52
25	Research Site	Pardubice		Czech Republic	532 03
26	Research Site	Plzen		Czech Republic	323 00
27	Research Site	Praha 2		Czech Republic	12000
28	Research Site	Praha 5		Czech Republic	150 06
29	Research Site	Aarhus C		Denmark	8000
30	Research Site	Esbjerg		Denmark	6700
31	Research Site	Kobenhavn		Denmark	2100
32	Research Site	Helsinki		Finland	00290
33	Research Site	Tampere		Finland	33520
34	Research Site	Turku		Finland	20100
35	Research Site	Besancon		France	25030
36	Research Site	Bordeaux		France	33076
37	Research Site	Clermont-Ferrand		France	63003
38	Research Site	Creteil		France	94101
39	Research Site	Dijon		France	21033
40	Research Site	Lille		France	59037
41	Research Site	Lyon		France	69677
42	Research Site	Marseille		France	13385
43	Research Site	Nancy		France	54035
44	Research Site	Paris		France	75019
45	Research Site	Paris		France	75651
46	Research Site	Rennes		France	35033
47	Research Site	Strasbourg		France	67091
48	Research Site	Toulouse		France	31059
49	Research Site	Berlin		Germany	13347
50	Research Site	Essen		Germany	45122
51	Research Site	Gießen		Germany	35385
52	Research Site	Hannover		Germany	30625
53	Research Site	Hennigsdorf		Germany	16761
54	Research Site	München		Germany	81377
55	Research Site	Offenbach		Germany	63069
56	Research Site	Osnabrück		Germany	49076
57	Research Site	Regensburg		Germany	93053
58	Research Site	Rostock		Germany	18147
59	Research Site	Athens		Greece	11527
60	Research Site	Budapest		Hungary	1021
61	Research Site	Budapest		Hungary	1115
62	Research Site	Budapest		Hungary	1145
63	Research Site	Budapest		Hungary	1204
64	Research Site	Debrecen		Hungary	4012
65	Research Site	Debrecen		Hungary	4031
66	Research Site	Gyor		Hungary	9000
67	Research Site	Nyiregyhaza		Hungary	4400
68	Research Site	Szekesfehervar		Hungary	8000
69	Research Site	Dublin		Ireland	4
70	Research Site	Jerusalem		Israel	91120
71	Research Site	Tel Hashomer		Israel	52621
72	Research Site	Bari		Italy	70124
73	Research Site	Genova		Italy	16132
74	Research Site	Milano		Italy	20132
75	Research Site	Roma		Italy	00185
76	Research Site	Amsterdam		Netherlands	1081HV
77	Research Site	Breda		Netherlands	4818 CK
78	Research Site	Hertogenbosch		Netherlands	5211 NL
79	Research Site	Nieuwegein		Netherlands	3435 CM
80	Research Site	Nijmegen		Netherlands	6533 PA
81	Research Site	Rotterdam		Netherlands	3015 GD
82	Research Site	Auckland		New Zealand	1023
83	Research Site	Christchurch		New Zealand	8011
84	Research Site	Białystok		Poland	15-402
85	Research Site	Białystok		Poland	15-420
86	Research Site	Bydgoszcz		Poland	85-681
87	Research Site	Gdańsk		Poland	80-803
88	Research Site	Katowice		Poland	40-752
89	Research Site	Kraków		Poland	31-530
90	Research Site	Lodz		Poland	90-153
91	Research Site	Lublin		Poland	20-954
92	Research Site	Warsaw		Poland	02-957
93	Research Site	Warszawa		Poland	02-097
94	Research Site	Barcelona		Spain	08035
95	Research Site	Barcelona		Spain	08907
96	Research Site	Málaga		Spain	29010
97	Research Site	Goteborg		Sweden	41685
98	Research Site	Stockholm		Sweden	141 86
99	Research Site	Stockholm		Sweden	17176
100	Research Site	Basel		Switzerland	4031
101	Research Site	Ankara		Turkey	06100
102	Research Site	Istanbul		Turkey	34303
103	Research Site	Istanbul		Turkey	34390
104	Research Site	Essex		United Kingdom	RM7 0AG
105	Research Site	Liverpool		United Kingdom	L9 7AJ
106	Research Site	London		United Kingdom	E1 1BB
107	Research Site	London		United Kingdom	SE5 9RF
108	Research Site	London		United Kingdom	SW17 0QT
109	Research Site	Newcastle Upon Tyne		United Kingdom	NE14LP
110	Research Site	Oxford		United Kingdom	OX3 9DU
111	Research Site	Sheffield		United Kingdom	S10 2JF
112	Research Site	Stoke on Trent		United Kingdom	ST4 7LN

Sponsors and Collaborators

• Biogen

Investigators

• Study Director: Medical Director, Biogen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The website of the National Multiple Sclerosis Society, an organization dedicated to providing information to individuals with MS, their families, and healthcare providers.
• MSActiveSource.com is a resource for news, information, and disease management for all individuals touched by multiple sclerosis. This site is sponsored by Biogen Idec.

Publications

None provided.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT00297232
• Other Study ID Numbers: 101-MS-321
• First Posted: Feb 28, 2006
• Last Update Posted: Jul 15, 2016
• Last Verified: May 1, 2015

• Keywords provided by Biogen: Multiple Sclerosis; MS
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Natalizumab

Study Results

Participant Flow

Pre-assignment Detail	Participants from studies 101-MS-321 (NCT00297232) and 101-MS-322 (NCT00306592) are included in this presentation of combined final data. Note: In the Participant Flow table, 'progressive multifocal leukoencephalopathy' is abbreviated to 'PML'. and John Cunningham virus is abbreviated to 'JCV'.

Arm/Group Title	Natalizumab
Arm/Group Description	300 mg intravenous (IV) infusions once every 4 weeks for up to 480 weeks
Period Title: Overall Study
STARTED	1094
COMPLETED	489
NOT COMPLETED	605

Baseline Characteristics

Arm/Group Title	Natalizumab
Arm/Group Description	300 mg IV infusions once every 4 weeks for up to 480 weeks
Overall Participants	1094
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.4 (8.12)
Age, Customized (years) [Number]
20 to 29 years	98
30 to 39 years	347
40 to 49 years	454
50 to 59 years	195
Sex: Female, Male (Count of Participants)
Female	755 69%
Male	339 31%

Outcome Measures

1. Primary Outcome

Title	Time to 24-week Confirmed Expanded Disability Status Scale (EDSS) Progression
Description	Time to 24-week confirmed EDSS progression in participants with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 24-week EDSS progression was defined as ≥ 0.5 point increase from a baseline EDSS ≥ 6.0, or ≥ 1.0 point increase from a baseline EDSS ≥ 1.0 and < 6.0, or ≥ 1.5 point increase from a baseline EDSS of 0, all sustained for 24 weeks.
Time Frame	up to 480 weeks

Outcome Measure Data

Analysis Population Description

Participants with EDSS progression (regardless of length of follow-up) sustained for 24 weeks.

Arm/Group Title	Natalizumab
Arm/Group Description	300 mg IV infusions once every 4 weeks for up to 480 weeks
Measure Participants	220
Median (Inter-Quartile Range) [weeks]	121.9

2. Primary Outcome

Title	Time to 48-week Confirmed EDSS Progression
Description	Time to 48-week confirmed EDSS progression in particpants with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 48-week EDSS progression was defined as ≥ 0.5 point increase from a baseline EDSS ≥ 6.0, or ≥ 1.0 point increase from a baseline EDSS ≥ 1.0 and < 6.0, or ≥ 1.5 point increase from a baseline EDSS of 0, all sustained for 48 weeks.
Time Frame	up to 480 weeks

Outcome Measure Data

Analysis Population Description

Participants with EDSS progression (regardless of length of follow-up) sustained for 48 weeks.

Arm/Group Title	Natalizumab
Arm/Group Description	300 mg IV infusions once every 4 weeks for up to 480 weeks
Measure Participants	181
Median (Inter-Quartile Range) [weeks]	130.1

3. Primary Outcome

Title	Time to 24-week Confirmed EDSS Improvement Where Baseline ≥ 2.0
Description	Time to 24-week confirmed EDSS improvement in subjects with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 24-week EDSS improvement is defined as ≥ 1.0 point decrease from baseline sustained for 24 weeks.
Time Frame	Up to 480 weeks

Outcome Measure Data

Analysis Population Description

Participants with EDSS improvement (regardless of length of follow-up) sustained for 24 weeks.

Arm/Group Title	Natalizumab
Arm/Group Description	300 mg IV infusions once every 4 weeks for up to 480 weeks
Measure Participants	173
Median (Inter-Quartile Range) [weeks]	48.1

Adverse Events

Time Frame	Serious adverse events (SAEs) were collected from screening through the follow-up (492 weeks). Non-serious AEs were collected from baseline through Week 264.
Arm/Group Title	Natalizumab
Arm/Group Description	300 mg IV infusions once every 4 weeks for up to 480 weeks
All Cause Mortality
	Natalizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Natalizumab
	Affected / at Risk (%)	# Events
Total	231/1094 (21.1%)
Blood and lymphatic system disorders
Anaemia	1/1094 (0.1%)
Coombs negative haemolytic anaemia	1/1094 (0.1%)
Immune thrombocytopenic purpura	1/1094 (0.1%)
Splenomegaly	1/1094 (0.1%)
Cardiac disorders
Atrial fibrillation	2/1094 (0.2%)
Myocardial infarction	2/1094 (0.2%)
Angina pectoris	1/1094 (0.1%)
Coronary artery occlusion	1/1094 (0.1%)
Coronary artery stenosis	1/1094 (0.1%)
Myocardial fibrosis	1/1094 (0.1%)
Sinus tachycardia	1/1094 (0.1%)
Congenital, familial and genetic disorders
Congenital anomaly	1/1094 (0.1%)
Endocrine disorders
Goitre	1/1094 (0.1%)
Hyperthyroidism	1/1094 (0.1%)
Eye disorders
Eye swelling	1/1094 (0.1%)
Glaucoma	1/1094 (0.1%)
Retinal tear	1/1094 (0.1%)
Vision blurred	1/1094 (0.1%)
Gastrointestinal disorders
Haemorrhoids	3/1094 (0.3%)
Abdominal adhesions	2/1094 (0.2%)
Abdominal pain	2/1094 (0.2%)
Anal fissure	2/1094 (0.2%)
Constipation	2/1094 (0.2%)
Intestinal obstruction	2/1094 (0.2%)
Abdominal hernia	1/1094 (0.1%)
Abdominal pain upper	1/1094 (0.1%)
Colitis ischaemic	1/1094 (0.1%)
Diarrhoea	1/1094 (0.1%)
Diverticular perforation	1/1094 (0.1%)
Duodenitis	1/1094 (0.1%)
Faecaloma	1/1094 (0.1%)
Flatulence	1/1094 (0.1%)
Functional gastrointestinal disorder	1/1094 (0.1%)
Gastric ulcer haemorrhage	1/1094 (0.1%)
Ileus	1/1094 (0.1%)
Inguinal hernia	1/1094 (0.1%)
Irritable bowel syndrome	1/1094 (0.1%)
Large intestine polyp	1/1094 (0.1%)
Oesophageal ulcer	1/1094 (0.1%)
Proctalgia	1/1094 (0.1%)
Rectal prolapse	1/1094 (0.1%)
Small intestinal obstruction	1/1094 (0.1%)
Umbilical hernia	1/1094 (0.1%)
General disorders
Pyrexia	2/1094 (0.2%)
Chest pain	1/1094 (0.1%)
Fatigue	1/1094 (0.1%)
Multi-organ failure	1/1094 (0.1%)
Oedema	1/1094 (0.1%)
Pain	1/1094 (0.1%)
Polyp	1/1094 (0.1%)
Hepatobiliary disorders
Cholelithiasis	5/1094 (0.5%)
Cholecystitis	2/1094 (0.2%)
Bile duct stone	1/1094 (0.1%)
Cholecystitis acute	1/1094 (0.1%)
Cholecystitis chronic	1/1094 (0.1%)
Immune system disorders
Immune reconstitution inflammatory syndrome	11/1094 (1%)
Anaphylactic shock	2/1094 (0.2%)
Hypersensitivity	2/1094 (0.2%)
Anaphylactic reaction	1/1094 (0.1%)
Drug hypersensitivity	1/1094 (0.1%)
Infections and infestations
Progressive multifocal leukoencephalopathy	18/1094 (1.6%)
Urinary tract infection	13/1094 (1.2%)
Pneumonia	4/1094 (0.4%)
Gastroenteritis	3/1094 (0.3%)
Bronchitis viral	2/1094 (0.2%)
Cystitis	2/1094 (0.2%)
Influenza	2/1094 (0.2%)
Staphylococcal infection	2/1094 (0.2%)
Appendicitis	1/1094 (0.1%)
Atypical pneumonia	1/1094 (0.1%)
Bronchitis	1/1094 (0.1%)
Bronchopneumonia	1/1094 (0.1%)
Catheter site infection	1/1094 (0.1%)
Cellulitis	1/1094 (0.1%)
Device related sepsis	1/1094 (0.1%)
Diverticulitis	1/1094 (0.1%)
Epididymitis	1/1094 (0.1%)
Gastroenteritis viral	1/1094 (0.1%)
Hepatitis A	1/1094 (0.1%)
Herpes zoster	1/1094 (0.1%)
Lower respiratory tract infection viral	1/1094 (0.1%)
Lung infection	1/1094 (0.1%)
Meningitis viral	1/1094 (0.1%)
Nasopharyngitis	1/1094 (0.1%)
Oral candidiasis	1/1094 (0.1%)
Pelvic inflammatory disease	1/1094 (0.1%)
Peritonitis	1/1094 (0.1%)
Pharyngitis	1/1094 (0.1%)
Pneumonia pneumococcal	1/1094 (0.1%)
Pneumonia streptococcal	1/1094 (0.1%)
Pyelonephritis	1/1094 (0.1%)
Sinusitis	1/1094 (0.1%)
Tooth abscess	1/1094 (0.1%)
Wound infection	1/1094 (0.1%)
Injury, poisoning and procedural complications
Fall	7/1094 (0.6%)
Head injury	4/1094 (0.4%)
Lower limb fracture	3/1094 (0.3%)
Concussion	2/1094 (0.2%)
Facial bones fracture	2/1094 (0.2%)
Humerus fracture	2/1094 (0.2%)
Road traffic accident	2/1094 (0.2%)
Wrist fracture	2/1094 (0.2%)
Accidental overdose	1/1094 (0.1%)
Animal bite	1/1094 (0.1%)
Ankle fracture	1/1094 (0.1%)
Arteriovenous fistula site complication	1/1094 (0.1%)
Arthropod bite	1/1094 (0.1%)
Face injury	1/1094 (0.1%)
Femur fracture	1/1094 (0.1%)
Fibula fracture	1/1094 (0.1%)
Foot fracture	1/1094 (0.1%)
Gun shot wound	1/1094 (0.1%)
Hip fracture	1/1094 (0.1%)
Laceration	1/1094 (0.1%)
Lumbar vertebral fracture	1/1094 (0.1%)
Post procedural haemorrhage	1/1094 (0.1%)
Rib fracture	1/1094 (0.1%)
Tendon rupture	1/1094 (0.1%)
Traumatic intracranial haemorrhage	1/1094 (0.1%)
Ulna fracture	1/1094 (0.1%)
Investigations
Blood pressure increased	1/1094 (0.1%)
Polyomavirus test positive	1/1094 (0.1%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/1094 (0.1%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	5/1094 (0.5%)
Osteoarthritis	3/1094 (0.3%)
Arthralgia	2/1094 (0.2%)
Spinal column stenosis	2/1094 (0.2%)
Arthritis	1/1094 (0.1%)
Back pain	1/1094 (0.1%)
Bursitis	1/1094 (0.1%)
Joint instability	1/1094 (0.1%)
Joint stiffness	1/1094 (0.1%)
Muscular weakness	1/1094 (0.1%)
Musculoskeletal disorder	1/1094 (0.1%)
Osteonecrosis	1/1094 (0.1%)
Rotator cuff syndrome	1/1094 (0.1%)
Spinal osteoarthritis	1/1094 (0.1%)
Tenosynovitis	1/1094 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	5/1094 (0.5%)
Malignant melanoma	5/1094 (0.5%)
Uterine leiomyoma	5/1094 (0.5%)
Intraductal proliferative breast lesion	3/1094 (0.3%)
Breast cancer	2/1094 (0.2%)
Adenocarcinoma of salivary gland	1/1094 (0.1%)
Bile duct adenocarcinoma	1/1094 (0.1%)
Bladder transitional cell carcinoma	1/1094 (0.1%)
Cerebellopontine angle tumour	1/1094 (0.1%)
Colon cancer	1/1094 (0.1%)
Invasive ductal breast carcinoma	1/1094 (0.1%)
Lobular breast carcinoma in situ	1/1094 (0.1%)
Lung adenocarcinoma	1/1094 (0.1%)
Lung neoplasm malignant	1/1094 (0.1%)
Meningioma	1/1094 (0.1%)
Metastatic malignant melanoma	1/1094 (0.1%)
Prostate cancer	1/1094 (0.1%)
Teratoma	1/1094 (0.1%)
Thyroid adenoma	1/1094 (0.1%)
Nervous system disorders
Multiple sclerosis relapse	21/1094 (1.9%)
Multiple sclerosis	2/1094 (0.2%)
Transient ischaemic attack	2/1094 (0.2%)
Trigeminal neuralgia	2/1094 (0.2%)
Altered state of consciousness	1/1094 (0.1%)
Amnesia	1/1094 (0.1%)
Cerebral cyst	1/1094 (0.1%)
Cerebrovascular insufficiency	1/1094 (0.1%)
Convulsion	1/1094 (0.1%)
Encephalopathy	1/1094 (0.1%)
Epilepsy	1/1094 (0.1%)
Facial neuralgia	1/1094 (0.1%)
Headache	1/1094 (0.1%)
Hypoxic-ischaemic encephalopathy	1/1094 (0.1%)
Migraine	1/1094 (0.1%)
Sciatica	1/1094 (0.1%)
Pregnancy, puerperium and perinatal conditions
Abortion missed	2/1094 (0.2%)
Abortion spontaneous	1/1094 (0.1%)
Foetal death	1/1094 (0.1%)
Haemorrhage in pregnancy	1/1094 (0.1%)
Premature baby	1/1094 (0.1%)
Psychiatric disorders
Depression	4/1094 (0.4%)
Suicide attempt	3/1094 (0.3%)
Completed suicide	2/1094 (0.2%)
Mania	2/1094 (0.2%)
Suicidal ideation	2/1094 (0.2%)
Abnormal behaviour	1/1094 (0.1%)
Anxiety disorder	1/1094 (0.1%)
Bipolar I disorder	1/1094 (0.1%)
Confusional state	1/1094 (0.1%)
Obsessive-compulsive disorder	1/1094 (0.1%)
Psychotic disorder	1/1094 (0.1%)
Schizophrenia	1/1094 (0.1%)
Renal and urinary disorders
Renal colic	3/1094 (0.3%)
Haematuria	1/1094 (0.1%)
Neurogenic bladder	1/1094 (0.1%)
Renal failure acute	1/1094 (0.1%)
Urinary retention	1/1094 (0.1%)
Reproductive system and breast disorders
Metrorrhagia	2/1094 (0.2%)
Uterine polyp	2/1094 (0.2%)
Adnexal torsion	1/1094 (0.1%)
Breast hyperplasia	1/1094 (0.1%)
Breast mass	1/1094 (0.1%)
Cervical dysplasia	1/1094 (0.1%)
Menometrorrhagia	1/1094 (0.1%)
Menorrhagia	1/1094 (0.1%)
Ovarian cyst	1/1094 (0.1%)
Rectocele	1/1094 (0.1%)
Vaginal prolapse	1/1094 (0.1%)
Respiratory, thoracic and mediastinal disorders
Nasal polyps	2/1094 (0.2%)
Aspiration	1/1094 (0.1%)
Asthma	1/1094 (0.1%)
Chronic obstructive pulmonary disease	1/1094 (0.1%)
Obstructive airways disorder	1/1094 (0.1%)
Pleural effusion	1/1094 (0.1%)
Pneumonia aspiration	1/1094 (0.1%)
Pneumothorax	1/1094 (0.1%)
Pulmonary embolism	1/1094 (0.1%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/1094 (0.1%)
Melanocytic hyperplasia	1/1094 (0.1%)
Skin disorder	1/1094 (0.1%)
Surgical and medical procedures
Peripheral nerve decompression	1/1094 (0.1%)
Spinal laminectomy	1/1094 (0.1%)
Thyroid nodule removal	1/1094 (0.1%)
Vascular graft	1/1094 (0.1%)
Vascular disorders
Deep vein thrombosis	2/1094 (0.2%)
Peripheral ischaemia	1/1094 (0.1%)
Thrombophlebitis	1/1094 (0.1%)
Venous stenosis	1/1094 (0.1%)
Other (Not Including Serious) Adverse Events
	Natalizumab
	Affected / at Risk (%)	# Events
Total	752/1094 (68.7%)
Gastrointestinal disorders
Diarrhoea	80/1094 (7.3%)
General disorders
Fatigue	102/1094 (9.3%)
Infections and infestations
Nasopharyngitis	256/1094 (23.4%)
Upper respiratory tract infection	192/1094 (17.6%)
Urinary tract infection	162/1094 (14.8%)
Influenza	122/1094 (11.2%)
Sinusitis	82/1094 (7.5%)
Bronchitis	67/1094 (6.1%)
Injury, poisoning and procedural complications
Fall	61/1094 (5.6%)
Musculoskeletal and connective tissue disorders
Back pain	113/1094 (10.3%)
Arthralgia	86/1094 (7.9%)
Pain in extremity	62/1094 (5.7%)
Nervous system disorders
Multiple sclerosis relapse	164/1094 (15%)
Headache	157/1094 (14.4%)
Dizziness	62/1094 (5.7%)
Psychiatric disorders
Depression	72/1094 (6.6%)

Limitations/Caveats

Sponsor decided to terminate the study prior to all subjects reaching Week 480 as the primary objective was deemed to have been met and only approximately 45% of the original STRATA population remained in the study at the time of study termination.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.